Skip to main content
SpringerLink
Log in
Book cover

Systems Biology of Tumor Dormancy pp 91–107Cite as

Tumor Dormancy, Oncogene Addiction, Cellular Senescence, and Self-Renewal Programs

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 734))

Abstract

Cancers are frequently addicted to initiating oncogenes that elicit aberrant cellular proliferation, self-renewal, and apoptosis. Restoration of oncogenes to normal physiologic regulation can elicit dramatic reversal of the neoplastic phenotype, including reduced proliferation and increased apoptosis of tumor cells (Science 297(5578):63–64, 2002). In some cases, oncogene inactivation is associated with compete elimination of a tumor. However, in other cases, oncogene inactivation induces a conversion of tumor cells to a dormant state that is associated with cellular differentiation and/or loss of the ability to self-replicate. Importantly, this dormant state is reversible, with tumor cells regaining the ability to self-renew upon oncogene reactivation. Thus, understanding the mechanism of oncogene inactivation-induced dormancy may be crucial for predicting therapeutic outcome of targeted therapy. One important mechanistic insight into tumor dormancy is that oncogene addiction might involve regulation of a decision between self-renewal and cellular senescence. Recent evidence suggests that this decision is regulated by multiple mechanisms that include tumor cell-intrinsic, cell-autonomous mechanisms and host-dependent, tumor cell-non-autonomous programs (Mol Cell 4(2):199–207, 1999; Science 297(5578):102–104, 2002; Nature 431(7012):1112–1117, 2004; Proc Natl Acad Sci U S A 104(32):13028–13033, 2007). In particular, the tumor microenvironment, which is known to be critical during tumor initiation (Cancer Cell 7(5):411–423, 2005; J Clin Invest 121(6):2436–2446, 2011), prevention (Nature 410(6832):1107–1111, 2001), and progression (Cytokine Growth Factor Rev 21(1):3–10, 2010), also appears to dictate when oncogene inactivation elicits the permanent loss of self-renewal through induction of cellular senescence (Nat Rev Clin Oncol 8(3):151–160, 2011; Science 313(5795):1960–1964, 2006; N Engl J Med 351(21):2159–21569, 2004). Thus, oncogene addiction may be best modeled as a consequence of the interplay amongst cell-autonomous and host-dependent programs that define when a therapy will result in tumor dormancy.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Weinstein IB (2002) Cancer. Addiction to oncogenes—the Achilles heal of cancer. Science 297(5578):63–64

    Article  PubMed  CAS  Google Scholar 

  2. Felsher DW, Bishop JM (1999) Reversible tumorigenesis by MYC in hematopoietic lineages. Mol Cell 4(2):199–207

    Article  PubMed  CAS  Google Scholar 

  3. Jain M et al (2002) Sustained loss of a neoplastic phenotype by brief inactivation of MYC. Science 297(5578):102–104

    Article  PubMed  CAS  Google Scholar 

  4. Shachaf CM et al (2004) MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature 431(7012):1112–1117

    Article  PubMed  CAS  Google Scholar 

  5. Wu CH et al (2007) Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation. Proc Natl Acad Sci U S A 104(32):13028–13033

    Article  PubMed  CAS  Google Scholar 

  6. de Visser KE, Korets LV, Coussens LM (2005) De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell 7(5):411–423

    Article  PubMed  CAS  Google Scholar 

  7. Dougan M et al (2011) A dual role for the immune response in a mouse model of inflammation-associated lung cancer. J Clin Invest 121(6):2436–2446

    Article  PubMed  CAS  Google Scholar 

  8. Shankaran V et al (2001) IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410(6832):1107–1111

    Article  PubMed  CAS  Google Scholar 

  9. Ruffell B et al (2010) Lymphocytes in cancer development: polarization towards pro-tumor immunity. Cytokine Growth Factor Rev 21(1):3–10

    Article  PubMed  CAS  Google Scholar 

  10. Zitvogel L, Kepp O, Kroemer G (2011) Immune parameters affecting the efficacy of chemotherapeutic regimens. Nat Rev Clin Oncol 8(3):151–160

    Article  PubMed  CAS  Google Scholar 

  11. Galon J et al (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313(5795):1960–1964

    Article  PubMed  CAS  Google Scholar 

  12. Dave SS et al (2004) Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med 351(21):2159–2169

    Article  PubMed  CAS  Google Scholar 

  13. Felsher DW (2003) Cancer revoked: oncogenes as therapeutic targets. Nat Rev Cancer 3(5):375–380

    Article  PubMed  CAS  Google Scholar 

  14. Weinstein IB, Joe A (2008) Oncogene addiction. Cancer Res 68(9):3077–3080; discussion 3080

    Google Scholar 

  15. Sharma SV, Settleman J (2007) Oncogene addiction: setting the stage for molecularly targeted cancer therapy. Genes Dev 21(24):3214–3231

    Article  PubMed  CAS  Google Scholar 

  16. Huettner CS et al (2000) Reversibility of acute B-cell leukaemia induced by BCR-ABL1. Nat Genet 24(1):57–60

    Article  PubMed  CAS  Google Scholar 

  17. Chin L et al (1999) Essential role for oncogenic Ras in tumour maintenance. Nature 400(6743):468–472

    Article  PubMed  CAS  Google Scholar 

  18. Hoeflich KP et al (2006) Oncogenic BRAF is required for tumor growth and maintenance in melanoma models. Cancer Res 66(2):999–1006

    Article  PubMed  CAS  Google Scholar 

  19. Boxer RB et al (2004) Lack of sustained regression of c-MYC-induced mammary adenocarcinomas following brief or prolonged MYC inactivation. Cancer Cell 6(6):577–586

    Article  PubMed  CAS  Google Scholar 

  20. Giuriato S et al (2006) Sustained regression of tumors upon MYC inactivation requires p53 or thrombospondin-1 to reverse the angiogenic switch. Proc Natl Acad Sci USA 103(44): 16266–16271

    Article  PubMed  CAS  Google Scholar 

  21. Shchors K et al (2006) The Myc-dependent angiogenic switch in tumors is mediated by interleukin 1beta. Genes Dev 20(18):2527–2538

    Article  PubMed  CAS  Google Scholar 

  22. Tran PT et al (2008) Combined inactivation of MYC and K-Ras oncogenes reverses tumorigenesis in lung adenocarcinomas and lymphomas. PLoS One 3(5):e2125

    Article  PubMed  CAS  Google Scholar 

  23. Hait WN, Hambley TW (2009) Targeted cancer therapeutics. Cancer Res 69(4):1263–1267; discussion 1267

    Google Scholar 

  24. Sawyers C (2004) Targeted cancer therapy. Nature 432(7015):294–297

    Article  PubMed  CAS  Google Scholar 

  25. Druker BJ et al (2001) Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344(14):1031–1037

    Article  PubMed  CAS  Google Scholar 

  26. Hudis CA (2007) Trastuzumab—mechanism of action and use in clinical practice. N Engl J Med 357(1):39–51

    Article  PubMed  CAS  Google Scholar 

  27. Chapman PB et al (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364(26):2507–2516

    Article  PubMed  CAS  Google Scholar 

  28. Cataldo VD et al (2011) Treatment of non-small-cell lung cancer with erlotinib or gefitinib. N Engl J Med 364(10):947–955

    Article  PubMed  CAS  Google Scholar 

  29. Felsher DW (2004) Reversibility of oncogene-induced cancer. Curr Opin Genet Dev 14(1):37–42

    Article  PubMed  CAS  Google Scholar 

  30. Sharma SV, Settleman J (2006) Oncogenic shock: turning an activated kinase against the tumor cell. Cell Cycle 5(24):2878–2880

    Article  PubMed  CAS  Google Scholar 

  31. Kaelin WG Jr (2005) The concept of synthetic lethality in the context of anticancer therapy. Nat Rev Cancer 5(9):689–698

    Article  PubMed  CAS  Google Scholar 

  32. Albini A, Sporn MB (2007) The tumour microenvironment as a target for chemoprevention. Nat Rev Cancer 7(2):139–147

    Article  PubMed  CAS  Google Scholar 

  33. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674

    Article  PubMed  CAS  Google Scholar 

  34. Coussens LM et al (2000) MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 103(3):481–490

    Article  PubMed  CAS  Google Scholar 

  35. Bissell MJ, Radisky D (2001) Putting tumours in context. Nat Rev Cancer 1(1):46–54

    Article  PubMed  CAS  Google Scholar 

  36. Choi PS et al (2011) Lymphomas that recur after MYC suppression continue to exhibit oncogene addiction. Proc Natl Acad Sci U S A 108(42):17432–17437

    Article  PubMed  CAS  Google Scholar 

  37. Gorre ME et al (2001) Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293(5531):876–880

    Article  PubMed  CAS  Google Scholar 

  38. Pao W et al (2005) KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2(1):e17

    Article  PubMed  CAS  Google Scholar 

  39. Aguirre-Ghiso JA (2007) Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer 7(11):834–846

    Article  PubMed  CAS  Google Scholar 

  40. Felsher DW (2010) MYC inactivation elicits oncogene addiction through both tumor cell-intrinsic and host-dependent mechanisms. Genes Cancer 1(6):597–604

    Article  PubMed  CAS  Google Scholar 

  41. Nardella C et al (2011) Pro-senescence therapy for cancer treatment. Nat Rev Cancer 11(7):503–511

    Article  PubMed  CAS  Google Scholar 

  42. Felsher DW (2008) Reversing cancer from inside and out: oncogene addiction, cellular senescence, and the angiogenic switch. Lymphat Res Biol 6(3–4):149–154

    Article  PubMed  Google Scholar 

  43. Felsher DW (2008) Tumor dormancy and oncogene addiction. APMIS 116(7–8):629–637

    Article  PubMed  CAS  Google Scholar 

  44. Bishop JM (1991) Molecular themes in oncogenesis. Cell 64(2):235–248

    Article  PubMed  CAS  Google Scholar 

  45. Reya T et al (2001) Stem cells, cancer, and cancer stem cells. Nature 414(6859):105–111

    Article  PubMed  CAS  Google Scholar 

  46. Dick JE (2008) Stem cell concepts renew cancer research. Blood 112(13):4793–4807

    Article  PubMed  CAS  Google Scholar 

  47. Wang JC, Dick JE (2005) Cancer stem cells: lessons from leukemia. Trends Cell Biol 15(9):494–501

    Article  PubMed  CAS  Google Scholar 

  48. Sell S (2004) Stem cell origin of cancer and differentiation therapy. Crit Rev Oncol Hematol 51(1):1–28

    Article  PubMed  Google Scholar 

  49. Nguyen LV et al (2012) Cancer stem cells: an evolving concept. Nat Rev Cancer 12(2):133–143

    PubMed  CAS  Google Scholar 

  50. Das B et al (2009) The idea and evidence for the tumor stemness switch. In: Rajasekhar V, Vemuri M (eds) Regulatory networks in stem cells. Humana Press, New York, pp 473–487

    Chapter  Google Scholar 

  51. Zheng H et al (2008) Pten and p53 converge on c-Myc to control differentiation, self-renewal, and transformation of normal and neoplastic stem cells in glioblastoma. Cold Spring Harb Symp Quant Biol 73:427–437

    Article  PubMed  CAS  Google Scholar 

  52. Wang J et al (2008) c-Myc is required for maintenance of glioma cancer stem cells. PLoS One 3(11):e3769

    Article  PubMed  CAS  Google Scholar 

  53. Marquardt JU et al (2011) Human hepatic cancer stem cells are characterized by common stemness traits and diverse oncogenic pathways. Hepatology 54(3):1031–1042

    Article  PubMed  CAS  Google Scholar 

  54. Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25:585–621

    Article  PubMed  CAS  Google Scholar 

  55. Hayflick L (1965) The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37:614–636

    Article  PubMed  CAS  Google Scholar 

  56. Lundblad V, Szostak JW (1989) A mutant with a defect in telomere elongation leads to senescence in yeast. Cell 57(4):633–643

    Article  PubMed  CAS  Google Scholar 

  57. Yu GL et al (1990) In vivo alteration of telomere sequences and senescence caused by mutated tetrahymena telomerase RNAs. Nature 344(6262):126–132

    Article  PubMed  CAS  Google Scholar 

  58. Chen Q, Ames BN (1994) Senescence-like growth arrest induced by hydrogen peroxide in human diploid fibroblast F65 cells. Proc Natl Acad Sci U S A 91(10):4130–4134

    Article  PubMed  CAS  Google Scholar 

  59. Di Leonardo A et al (1994) DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts. Genes Dev 8(21):2540–2551

    Article  PubMed  Google Scholar 

  60. Schmitt CA et al (2002) A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell 109(3):335–346

    Article  PubMed  CAS  Google Scholar 

  61. Chang BD et al (1999) A senescence-like phenotype distinguishes tumor cells that undergo terminal proliferation arrest after exposure to anticancer agents. Cancer Res 59(15):3761–3767

    PubMed  CAS  Google Scholar 

  62. Michishita E et al (1999) 5-Bromodeoxyuridine induces senescence-like phenomena in mammalian cells regardless of cell type or species. J Biochem 126(6):1052–1059

    Article  PubMed  CAS  Google Scholar 

  63. O’Brien W, Stenman G, Sager R (1986) Suppression of tumor growth by senescence in virally transformed human fibroblasts. Proc Natl Acad Sci U S A 83(22):8659–8663

    Article  PubMed  Google Scholar 

  64. Serrano M et al (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88(5):593–602

    Article  PubMed  CAS  Google Scholar 

  65. Zhu J et al (1998) Senescence of human fibroblasts induced by oncogenic Raf. Genes Dev 12(19):2997–3007

    Article  PubMed  CAS  Google Scholar 

  66. Braig M et al (2005) Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 436(7051):660–665

    Article  PubMed  CAS  Google Scholar 

  67. Dimri GP et al (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 92(20):9363–9367

    Article  PubMed  CAS  Google Scholar 

  68. Narita M et al (2003) Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113(6):703–716

    Article  PubMed  CAS  Google Scholar 

  69. Collado M et al (2005) Tumour biology: senescence in premalignant tumours. Nature 436(7051):642

    Article  PubMed  CAS  Google Scholar 

  70. Chan HM et al (2005) The p400 E1A-associated protein is a novel component of the p53 –>  p21 senescence pathway. Genes Dev 19(2):196–201

    Article  PubMed  CAS  Google Scholar 

  71. Chen Z et al (2005) Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 436(7051):725–730

    Article  PubMed  CAS  Google Scholar 

  72. van Riggelen J et al (2010) The interaction between Myc and Miz1 is required to antagonize TGFbeta-dependent autocrine signaling during lymphoma formation and maintenance. Genes Dev 24(12):1281–1294

    Article  PubMed  CAS  Google Scholar 

  73. Reimann M et al (2010) Tumor stroma-derived TGF-beta limits Myc-driven lymphomagenesis via Suv39h1-dependent senescence. Cancer Cell 17(3):262–272

    Article  PubMed  CAS  Google Scholar 

  74. Zhuang D et al (2008) C-MYC overexpression is required for continuous suppression of oncogene-induced senescence in melanoma cells. Oncogene 27(52):6623–6634

    Article  PubMed  CAS  Google Scholar 

  75. Lin AW et al (1998) Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling. Genes Dev 12(19):3008–3019

    Article  PubMed  CAS  Google Scholar 

  76. Rakhra K et al (2010) CD4(+) T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation. Cancer Cell 18(5):485–498

    Article  PubMed  CAS  Google Scholar 

  77. Xue W et al (2007) Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445(7128):656–660

    Article  PubMed  CAS  Google Scholar 

  78. Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357(9255):539–545

    Article  PubMed  CAS  Google Scholar 

  79. Dunn GP et al (2002) Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3(11):991–998

    Article  PubMed  CAS  Google Scholar 

  80. Schreiber RD, Old LJ, Smyth MJ (2011) Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 331(6024):1565–1570

    Article  PubMed  CAS  Google Scholar 

  81. de Visser KE, Eichten A, Coussens LM (2006) Paradoxical roles of the immune system during cancer development. Nat Rev Cancer 6(1):24–37

    Article  PubMed  CAS  Google Scholar 

  82. Andreu P et al (2010) FcRgamma activation regulates inflammation-associated squamous carcinogenesis. Cancer Cell 17(2):121–134

    Article  PubMed  CAS  Google Scholar 

  83. Girardi M et al (2004) Characterizing the protective component of the alphabeta T cell response to transplantable squamous cell carcinoma. J Invest Dermatol 122(3):699–706

    Article  PubMed  CAS  Google Scholar 

  84. Lin EY et al (2001) Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med 193(6):727–740

    Article  PubMed  CAS  Google Scholar 

  85. Hung K et al (1998) The central role of CD4(+) T cells in the antitumor immune response. J Exp Med 188(12):2357–2368

    Article  PubMed  CAS  Google Scholar 

  86. Martin-Manso G et al (2008) Thrombospondin 1 promotes tumor macrophage recruitment and enhances tumor cell cytotoxicity of differentiated U937 cells. Cancer Res 68(17):7090–7099

    Article  PubMed  CAS  Google Scholar 

  87. Zhou P et al (2010) Mature B cells are critical to T-cell-mediated tumor immunity induced by an agonist anti-GITR monoclonal antibody. J Immunother 33(8):789–797

    Article  PubMed  CAS  Google Scholar 

  88. Wu J, Lanier LL (2003) Natural killer cells and cancer. Adv Cancer Res 90:127–156

    Article  PubMed  CAS  Google Scholar 

  89. DeNardo DG et al (2009) CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell 16(2):91–102

    Article  PubMed  CAS  Google Scholar 

  90. Condeelis J, Pollard JW (2006) Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 124(2):263–266

    Article  PubMed  CAS  Google Scholar 

  91. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867

    Article  PubMed  CAS  Google Scholar 

  92. Greten FR et al (2004) IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118(3):285–296

    Article  PubMed  CAS  Google Scholar 

  93. Ekbom A et al (1990) Ulcerative colitis and colorectal cancer. A population-based study. N Engl J Med 323(18):1228–1233

    Article  PubMed  CAS  Google Scholar 

  94. Wakabayashi O et al (2003) CD4+ T cells in cancer stroma, not CD8+ T cells in cancer cell nests, are associated with favorable prognosis in human non-small cell lung cancers. Cancer Sci 94(11):1003–1009

    Article  PubMed  CAS  Google Scholar 

  95. Zhang JP et al (2009) Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients. J Hepatol 50(5):980–989

    Article  PubMed  CAS  Google Scholar 

  96. Mantovani A et al (2008) Cancer-related inflammation. Nature 454(7203):436–444

    Article  PubMed  CAS  Google Scholar 

  97. Zhang H et al (2003) Concordant down-regulation of proto-oncogene PML and major histocompatibility antigen HLA class I expression in high-grade prostate cancer. Cancer Immun 3:2

    PubMed  Google Scholar 

  98. Zheng P et al (1998) Proto-oncogene PML controls genes devoted to MHC class I antigen presentation. Nature 396(6709):373–376

    Article  PubMed  CAS  Google Scholar 

  99. Sumimoto H et al (2006) The BRAF-MAPK signaling pathway is essential for cancer-immune evasion in human melanoma cells. J Exp Med 203(7):1651–1656

    Article  PubMed  CAS  Google Scholar 

  100. Boni A et al (2010) Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lymphocyte function. Cancer Res 70(13):5213–5219

    Article  PubMed  CAS  Google Scholar 

  101. Borrello MG et al (2005) Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene. Proc Natl Acad Sci U S A 102(41):14825–14830

    Article  PubMed  CAS  Google Scholar 

  102. Ancrile B, Lim KH, Counter CM (2007) Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis. Genes Dev 21(14):1714–1719

    Article  PubMed  CAS  Google Scholar 

  103. Sparmann A, Bar-Sagi D (2004) Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell 6(5):447–458

    Article  PubMed  CAS  Google Scholar 

  104. Sodir NM et al (2011) Endogenous Myc maintains the tumor microenvironment. Genes Dev 25(9):907–916

    Article  PubMed  CAS  Google Scholar 

  105. Boshoff C, Weiss R (2002) AIDS-related malignancies. Nat Rev Cancer 2(5):373–382

    Article  PubMed  CAS  Google Scholar 

  106. Ray-Coquard I et al (2009) Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res 69(13):5383–5391

    Article  PubMed  CAS  Google Scholar 

  107. Soucek L et al (2007) Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors. Nat Med 13(10):1211–1218

    Article  PubMed  CAS  Google Scholar 

  108. Shiao SL, Coussens LM (2010) The tumor-immune microenvironment and response to radiation therapy. J Mammary Gland Biol Neoplasia 15(4):411–421

    Article  PubMed  Google Scholar 

  109. Obeid M et al (2007) Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13(1):54–61

    Article  PubMed  CAS  Google Scholar 

  110. Restifo NP (2010) Can antitumor immunity help to explain “oncogene addiction”? Cancer Cell 18(5):403–405

    Article  PubMed  CAS  Google Scholar 

  111. Acosta JC et al (2008) Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133(6):1006–1018

    Article  PubMed  CAS  Google Scholar 

  112. Beatty G, Paterson Y (2001) IFN-gamma-dependent inhibition of tumor angiogenesis by tumor-infiltrating CD4+ T cells requires tumor responsiveness to IFN-gamma. J Immunol 166(4):2276–2282

    PubMed  CAS  Google Scholar 

  113. Kuilman T et al (2008) Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133(6):1019–1031

    Article  PubMed  CAS  Google Scholar 

  114. Muller-Hermelink N et al (2008) TNFR1 signaling and IFN-gamma signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis. Cancer Cell 13(6):507–518

    Article  PubMed  CAS  Google Scholar 

  115. Li SS et al (2002) T lymphocyte expression of thrombospondin-1 and adhesion to extracellular matrix components. Eur J Immunol 32(4):1069–1079

    Article  PubMed  CAS  Google Scholar 

  116. Li SS et al (2006) Endogenous thrombospondin-1 is a cell-surface ligand for regulation of integrin-dependent T-lymphocyte adhesion. Blood 108(9):3112–3120

    Article  PubMed  CAS  Google Scholar 

  117. Young GD, Murphy-Ullrich JE (2004) The tryptophan-rich motifs of the thrombospondin type 1 repeats bind VLAL motifs in the latent transforming growth factor-beta complex. J Biol Chem 279(46):47633–47642

    Article  PubMed  CAS  Google Scholar 

  118. Becker C et al (2004) TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity 21(4):491–501

    Article  PubMed  CAS  Google Scholar 

  119. Tang B et al (2007) Transforming growth factor-beta can suppress tumorigenesis through effects on the putative cancer stem or early progenitor cell and committed progeny in a breast cancer xenograft model. Cancer Res 67(18):8643–8652

    Article  PubMed  CAS  Google Scholar 

  120. Muranski P, Restifo NP (2009) Adoptive immunotherapy of cancer using CD4(+) T cells. Curr Opin Immunol 21(2):200–208

    Article  PubMed  CAS  Google Scholar 

  121. Gonzalez-Angulo AM, Hortobagyi GN, Ellis LM (2011) Targeted therapies: peaking beneath the surface of recent bevacizumab trials. Nat Rev Clin Oncol 8(6):319–320

    PubMed  Google Scholar 

  122. Wrzesinski C et al (2010) Increased intensity lymphodepletion enhances tumor treatment efficacy of adoptively transferred tumor-specific T cells. J Immunother 33(1):1–7

    Article  PubMed  Google Scholar 

  123. Tran PT et al (2011) Survival and death signals can predict tumor response to therapy after oncogene inactivation. Sci Transl Med 3(103):103ra99

    Article  PubMed  CAS  Google Scholar 

  124. Califano A (2011) Striking a balance between feasible and realistic biological models. Sci Transl Med 3(103):103ps39

    Article  PubMed  Google Scholar 

  125. Willmann JK et al (2008) Molecular imaging in drug development. Nat Rev Drug Discov 7(7):591–607

    Article  PubMed  CAS  Google Scholar 

  126. Pysz MA, Gambhir SS, Willmann JK (2010) Molecular imaging: current status and emerging strategies. Clin Radiol 65(7):500–516

    Article  PubMed  CAS  Google Scholar 

  127. Massoud TF, Gambhir SS (2003) Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 17(5):545–580

    Article  PubMed  CAS  Google Scholar 

  128. Nguyen QD, Aboagye EO (2010) Imaging the life and death of tumors in living subjects: preclinical PET imaging of proliferation and apoptosis. Integr Biol 2(10):483–495

    Article  Google Scholar 

  129. Michalski MH, Chen X (2011) Molecular imaging in cancer treatment. Eur J Nucl Med Mol Imaging 38(2):358–377

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge current members of the Felsher laboratory for critical discussion and previous members who have contributed to characterizing various models of oncogene addiction.

Author information

Authors and Affiliations

  1. Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, 269 Campus Drive, CCSR 1105, Stanford, CA, 94305-5151, USA

    David I. Bellovin PhD, Bikul Das MBBS, PhD & Dean W. Felsher MD, PhD

Authors
  1. David I. Bellovin PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bikul Das MBBS, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dean W. Felsher MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dean W. Felsher MD, PhD .

Editor information

Editors and Affiliations

  1. St. Elizabeth's Medical Center, Tufts University School of Medicine, 145 Harrison Avenue, Boston, 02135, Massachusetts, USA

    Heiko Enderling

  2. , Center of Cancer Systems Biology, Tufts University School of Medicine, 736 Cambridge Street, Boston, 02135, Massachusetts, USA

    Nava Almog

  3. , Center of Cancer Systems Biology, Tufts University School of Medicine, 736 Cambridge Street, Boston, 02135, Massachusetts, USA

    Lynn Hlatky

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Bellovin, D.I., Das, B., Felsher, D.W. (2013). Tumor Dormancy, Oncogene Addiction, Cellular Senescence, and Self-Renewal Programs. In: Enderling, H., Almog, N., Hlatky, L. (eds) Systems Biology of Tumor Dormancy. Advances in Experimental Medicine and Biology, vol 734. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1445-2_6

Download citation

Publish with us

Policies and ethics

Search

Navigation